Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells
Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells
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DOI：
10.4161/auto.28772
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发表时间：
2014-07-01
期刊：
影响因子：
13.3
通讯作者：
Chiu, Shu-Jun
中科院分区：
文献类型：
--
作者：
Huang, Yao-Huei;Yang, Pei-Ming;Chiu, Shu-Jun
电离辐射诱导细胞衰老以抑制癌细胞增殖。然而，它也通过释放促进肿瘤进展的衰老相关分泌表型（SASP）在未照射的邻近细胞中诱导有害的旁观者效应。虽然有报道称自噬促进衰老，但其作用仍不清楚。我们先前表明，辐射诱导PTTG 1缺失的癌细胞衰老。在这项研究中，我们发现自噬是PTTG 1缺失的乳腺癌细胞辐射诱导衰老所必需的。抑制自噬导致细胞从辐射诱导的衰老转变为凋亡。衰老的癌细胞通过释放CSF 2和随后激活JAK 2-STAT 3和AKT通路促进未照射细胞的侵袭和迁移来发挥旁观者效应。然而，辐射诱导的旁观者效应与抑制旁观者细胞中的内源性自噬相关，这也是由于CSF 2-JAK 2通路的激活。雷帕霉素诱导的自噬减少了辐射诱导的旁观者效应。这项研究首次揭示了自噬在辐射诱导的衰老和旁观者效应中的双重作用。
Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects.